Northern blot analysis shows that TCA3 is expressed after activation with either PMA/ionophore or high affinity IgE cross-linking in C57 cells. mRNA of TCA3 is induced within 2 hours, peaks at 3 hours, and disappears at 6 hours. Half-life of mRNA determined by adding actinomycin D is approximately 1/2 hour. These results demonstrate that TCA3 is regulated transcriptionally. Nuclear run-on assays show that the rate of TCA3 mRNA transcription is increased after activation consistent with transcriptional regulation. Promoter analysis confirmed that the TCA3 gene is regulated transcriptionally in mast cells, and that the minimal promoter sequences are contained within the 0.082 kb upstream region of the TCA3 gene with a putative enhancer NF-kB element between -0.324 kb and -0.136 kb and a putative inhibitory element between 1.324 kb and 2.0 kb upstream from the transcription start site. Functional assessment of the region between 1.324 kb and 2 kb demonstrated that there are at least two inhibitory elements. One is orientation independent. Comparative analysis of the promoter region of TCA3 in T cells and mast cells revealed different patterns of regulation. Direct mast cell-to-T cell interaction is required to induce transfected TCA3 CAT constructs in mast cells. Soluble mediators released by either unstimulated mast cells or cells stimulated by Fc(epsilon)RI cross-linking are not able to induce TCA3 CAT gene expression. Unstimulated mast cell pellets also are unable to direct expression of TCA3 CAT expression. Tissue distribution of TCA3 mRNA is limited to skeletal muscle in the normal mouse. No message was detected in the brain, liver, lung, spleen, heart, or kidney. I-309 (human homolog of TCA3) was also not detectable in those organs and lymph nodes. Mast cells chemotax to the chemokines RANTES and MCAF in a dose-dependent manner. Parallel studies demonstrate that this chemotaxis is not accompanied by mast cell histamine release. When mast cells are activated through Fc(epsilon)RI, chemotaxis can also be demonstrated to MIP-1alpha, and PF-4.